Alan T. Bates, MD, PhD, Gordon W. MacEwan, MD Health-supplement-exacerbated psychosis in Vancouver’s Downtown Eastside—not seeing the ephedra for the crystal meth: A case report When a patient presents with psychiatric disturbances, the physi- cian should ask about the use of supplements, even if the patient appears to have more serious problems with illegal drugs. ABSTRACT: The case of a woman supplement stores. However, since Case data whose psychotic illness was great- ephe drine was replaced by more A woman in her mid-forties, who gave ly exacerbated by ephedra demon- selective beta-agonists for treating informed consent for the publication strates the need for physicians to asthma in the 1930s, it has been of this case report, initially presented screen for use of health supplements, most commonly used as a fitness to psychiatric services with psychosis even in patients who appear to have and weight-loss supplement and not and labile affect. She was diagnosed more serious problems with illegal as a decongestant. In 2004 the Unit- as suffering from methamphetamine- drugs. This case also shows why ed States Food and Drug Adminis- induced psychosis, possibly with ephedra and ephedrine should be tration introduced a ban on ephedra- underlying bipolar disorder. She had more tightly managed in Canada. containing supplements and tightly been functioning relatively well until The ephedra plant (ma huang in Chi- regulated ephedrine after reports of age 40, when she broke up with a long- nese) has been used for medicinal serious adverse events, including term boyfriend, lost her apartment and purposes for thousands of years. Its severe psychiatric symptoms. In Can - vehicle, and wound up in shelter-like active ingredient, ephedrine, is a ada both substances remain readily accommodation in Vancouver’s close relative of amphetamine and available—a cause for concern given Downtown Eastside, where she began methamphetamine. Both ephedra the significant risk to health they using crystal meth. Even following a and ephedrine have been used as pose, especially in more vulnerable few involuntary admissions and depot decongestants in the past, and are populations. injection of the antipsychotic risperi- available for purchase in health done (Risperidal Consta), she fre- quently expressed anxiety about being persecuted by organized crime and women she believed were “running the city.” She also became very irritable, Dr Bates is a resident in the Psychiatry Department at the University of British Columbia. Dr MacEwan is a clinical associ- ate professor in the Psychiatry Department This article has been peer reviewed. at UBC. www.bcmj.org VOL. 54 NO. 9, NOVEMBER 2012 BC MEDICAL JOURNAL 465 Health-supplement-exacerbated psychosis in Vancouver’s Downtown Eastside sometimes confronting people on the cantly more organized, no longer ex - be taken orally, had a more prolonged street over “all the pornography and pressed persecutory delusions, was effect, and had greater chemical sta- garbage” she perceived to be around able to voluntarily enter a detox cen- bility.1 Eventually, it was replaced by the city. While her behavior could have tre, moved from shelter-like accom- more selective beta-agonists. been explained by methamphetamine- modation to more permanent housing, During the 1990s ephedra became induced psychosis, her symptoms did and returned to earning some income. widely used for fitness training and not occur in a temporal pattern that Though the cause of the patient’s psy- weight loss, and recreationally for its matched her crystal meth use. chosis was likely multifactorial, we stimulant effects. Some forms were The patient was very interested in believe the ephedra exacerbated her marketed to suggest they were ver- physical fitness and spent consider- condition, since the severity of her ill- sions of illegal substances (e.g., Her - able amounts of time lifting weights ness abated significantly when she bal Ecstasy)5 and were likely regard- and going for long walks. She often stopped using ephedra. ed as being safer because they were “natural,” despite a fivefold to twenty - fold variation in the ephedrine content of different supplements advertising equivalent doses.6 It is estimated that Though the cause of the patient’s 12.5 million US adults used ephedra between 1996 and 1998.7 psychosis was likely multifactorial, Along with adverse events such as we believe the ephedra exacerbated arrhythmia and stroke, psychiatric complications were common. The her condition, since the severity of most common psychiatric disturbanc - her illness abated significantly when es, in order, were psychosis, severe depression, mania/severe agitation, she stopped using ephedra. hallucinations, sleep disturbance, sui- cidal ideation, suicide attempt, and ephedra abuse/dependence. The major- ity of patients were women (60%), and most patients who experienced psy- complained of a racing heart during Discussion chiatric disturbances had taken ephed- physical activity, and was concerned Several species of shrubs are included ra for over 2 months (59%).8 Although that she was going to have a heart in the genus Ephedra. E. sinica, known ephedrine-induced psychosis is typi- attack. When questioned about her in Chinese as ma huang, has been used cally reversible with discontinuation, workout routines, she said she had for medicinal purposes in China for it can present after prolonged use or been using ephedra on and off since over 5000 years.1 The primary active after a single dose.3 Comorbid con- her twenties to give her increased ingredient, ephedrine, was first isolat- tributors to psychosis (e.g., primary energy. Contrary to Health Canada ed by Nagai in 1885 and then by psychotic illness, use of other stimu- guidelines, which allow the use of Merck in 1886.1 It is both an alpha- lants) are often present.3 ephedra as a decongestant for a maxi- and beta-adrenergic agonist and also Complaints about ephedra eventu- mum of 7 days, she had been trying to promotes norepinephrine and epine - ally led the US Food and Drug Admin- build physical endurance by using 8 to phrine release.2 The immediate CNS istration (FDA) to ban its use in 2004. 16 mg of ephedra daily for several stimulant effects of ephedrine result This was prompted in part by the death months. During this time she was able from promotion of dopamine release.3 of a professional baseball pitcher, to obtain a regular and cheap supply Systemically, ephedrine causes in - Steve Bechler of the Bal timore Ori- from a nearby health supplement store. creased peripheral resistance, heart oles, that was linked to ephedra use After being informed about the rate, and blood pressure, as well as and consolidated negative public opin- connection between her supplement urinary retention and bronchodilation.4 ion about its use.5 Despite the ban on use and her cardiac symptoms, she was Through the 1920s and 1930s, ephedra and tight regulation of ephed - convinced to discontinue the ephed ra. ephedrine replaced adrenaline for the rine in the United States, both ephedra Following this, she became signifi- treatment of asthma because it could and ephedrine remain readily avail- 466 BC MEDICAL JOURNAL VOL. 54 NO. 9, NOVEMBER 2012 www.bcmj.org Health-supplement-exacerbated psychosis in Vancouver’s Downtown Eastside able in Canada. For a little over $5 we were able to purchase a bottle of 50 8-mg tablets of ephedrine at a number of supplement stores in Vancouver. We had more difficulty finding ephed - Ephedrine and its botanical source ra powder, but did eventually find this ephedra are readily available in formulation for sale as well. legal, low-cost, “natural” stimulant Summary products in British Columbia, and are As a close relative of amphetamine and methamphetamine, ephedrine is known to cause psychosis, typically associated with significant risk of psy- reversible with discontinuation. chiatric symptoms. Ephedrine and its botanical source ephedra are readily available in legal, low-cost, “natural” stimulant products in British Colum- bia, and are known to cause psychosis, typically reversible with discontinua- tion. This case demonstrates the need 2. Lexicomp, Inc. Ephedra: Natural drug performance liquid chromatography. J to ask patients about health supple- information. In: Basow, DS (ed). UpTo- Pharm Sci 1998;87:1547-1553. ments, even pa tients who appear to Date. Waltham, MA: Walters Kluwer 7. Blanck HM, Khan LK, Serdula MK. Use of have more serious problems with ille- Health; 2011. nonprescription weight loss products: gal drugs. We believe Health Canada 3. Maglione M, Miotto K, Iguchi M, et al. Results from a multistate survey. JAMA should develop regulations more in Psychiatric symptoms associated with 2001;286:930-935. line with the American FDA. The pop- ephedra use. Expert Opin Drug Saf 2005; 8. Maglione M, Miotto K, Iguchi M, et al. ularity of ephedra and ephedrine clear- 4:879-884. Psychiatric effects of ephedra use: An ly poses a significant risk to health, 4. Jacobs KM, Hirsch KA. Psychiatric com- analysis of Food and Drug Administration especially in some more vulnerable plications of ma-huang. Psychosomatics reports of adverse events. Am J Psychi- populations. 2000;41:58-62. atry 2005;162:189-191. 5. Palamar J. How ephedrine escaped reg- Competing interests ulation in the United States: A historical None declared. review of misuse and associated policy. Health Policy 2011;99:1-9. References 6. Gurley BJ, Wang P, Gardner SF. 1. Lee MR. The history of ephedra (ma- Ephedrine-type alkaloid content of nutri- huang). J R Coll Physicians Edinb 2011; tional supplements containing Ephedra 41:78-84. sinica (ma-huang) as determined by high www.bcmj.org VOL. 54 NO. 9, NOVEMBER 2012 BC MEDICAL JOURNAL 467.